Cushing’s Syndrome

Overview – Cushing’s Syndrome

Cushing’s Syndrome refers to a clinical state of prolonged glucocorticoid excess, regardless of cause. It may result from exogenous steroid use or endogenous overproduction of cortisol. When specifically caused by an ACTH-secreting pituitary adenoma, it is referred to as Cushing’s Disease. This condition is associated with significant metabolic, cardiovascular, and musculoskeletal complications and must be recognised early to prevent morbidity.

Definition

• Cushing’s Syndrome: A collection of signs and symptoms resulting from chronic exposure to excess glucocorticoids.
• Cushing’s Disease: A subtype of Cushing’s Syndrome caused by an ACTH-producing pituitary adenoma (central cause).

Aetiology

• Exogenous (most common):
  • Prolonged corticosteroid therapy
• Endogenous causes:
  • Cushing’s Disease – ACTH-secreting pituitary adenoma
  • Ectopic ACTH production (e.g. small cell lung carcinoma)
  • Adrenal adenoma or carcinoma (ACTH-independent)

Pathophysiology (Cushing’s Disease)

• ACTH-secreting pituitary adenoma → ↑ACTH → Stimulates adrenal cortex → ↑Cortisol
• Cortisol excess exerts widespread effects on metabolism, blood pressure, immune function, and connective tissue.

Clinical Features

• Onset: Gradual
• Early signs:
  • Weight gain (especially central/truncal obesity)
  • Hypertension
• Classic features:
  • “Moon face” (facial rounding)
  • “Buffalo hump” (posterior cervical fat pad)
  • Abdominal striae (purple stretch marks)
  • Proximal muscle weakness
  • Thin skin & easy bruising
  • Hirsutism (in females)
  • Acne
  • Osteopenia/osteoporosis
  • Menstrual irregularities
  • Depression or psychosis
  • Insulin resistance → hyperglycaemia or type 2 diabetes

Investigations

• Initial screening:
  • 24hr urinary free cortisol
  • Midnight salivary cortisol
  • Low-dose dexamethasone suppression test
• To determine cause:
  • Serum ACTH levels:
    • ↑ACTH → ACTH-dependent (pituitary or ectopic source)
    • ↓ACTH → ACTH-independent (adrenal cause)
  • High-dose dexamethasone suppression test:
    • Suppression → Suggests pituitary (Cushing’s Disease)
    • No suppression → Suggests ectopic ACTH production
  • MRI brain → Pituitary tumour
  • CT adrenal glands → For suspected adrenal tumours

Management

• Exogenous Cushing’s Syndrome:
  • Gradual tapering of corticosteroids
• Cushing’s Disease (Pituitary Adenoma):
  • Trans-sphenoidal surgical resection
  • Temporary cortisol replacement post-op
  • Consider radiation or medical therapy if surgery fails
• Adrenal adenoma/carcinoma:
  • Surgical removal + cortisol replacement
• Ectopic ACTH production:
  • Identify and treat underlying tumour

Complications

• Type 2 diabetes mellitus
• Hypertension
• Osteoporosis
• Cardiovascular disease
• Opportunistic infections
• Adrenal insufficiency post-treatment

Summary – Cushing’s Syndrome

Cushing’s Syndrome is a condition of chronic glucocorticoid excess with systemic complications, most often iatrogenic in origin. Cushing’s Disease, caused by a pituitary adenoma, is a notable endogenous subtype. Diagnosis hinges on cortisol/ACTH levels and suppression testing, while management involves addressing the underlying source of hormone excess. For related conditions, visit our Endocrine Overview.